Modulus-tunable multifunctional hydrogel ink with nanofillers for 3D-Printed soft electronics.

Seamless integration and conformal contact of soft electronics with tissue surfaces have emerged as major challenges in realizing accurate monitoring of biological signals. However, the mechanical mismatch between the electronics and biological tissues impedes the conformal interfacing between them. Attempts have been made to utilize soft hydrogels as the bioelectronic materials to realize tissue-comfortable bioelectronics. However, hydrogels have several limitations in terms of their electrical and mechanical properties. In this study, we present the development of a 3D-printable modulus-tunable hydrogel with multiple functionalities. The hydrogel has a cross-linked double network, which greatly improves its mechanical properties. Functional fillers such as XLG or functionalized carbon nanotubes (fCNT) can be incorporated into the hydrogel to provide tunable mechanics (Young's modulus of 10-300 kPa) and electrical conductivity (electrical conductivity of ∼20 S/m). The developed hydrogel exhibits stretchability (∼1000% strain), self-healing ability (within 5 min), toughness (400-731 kJ/m3) viscoelasticity, tissue conformability, and biocompatibility. Upon examining the rheological properties in the modulated region, hydrogels can be 3D printed to customize the shape and design of the bioelectronics. These hydrogels can be fabricated into ring-shaped strain sensors for wearable sensor applications.

The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation.

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/ß-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/ß-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.

Restless legs syndrome in patients with obstructive sleep apnea: Association between apnea severity and symptoms of depression, insomnia, and daytime sleepiness.

OBJECTIVE: To determine if the prevalence and severity of restless legs syndrome (RLS) varies with apnea severity and analyze differences between the sexes in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness in patients with obstructive sleep apnea (OSA). METHODS: Symptoms of depression, insomnia, and daytime sleepiness were defined as Patient Health Questionnaire-9 score ≥10, Insomnia Severity Index score ≥15, and Epworth Sleepiness Scale score ≥11. Multivariate logistic and linear regression analyses were conducted. RESULTS: In 707 adults with OSA (85.1% males), 16.1% (n = 114) had comorbid RLS. The prevalence of RLS was markedly lower in those with moderate and severe OSA than in those with mild OSA. Similarly, the odds of RLS significantly decreased with increasing apnea-hypopnea index. After controlling for age and sex, in patients with comorbid RLS, the International RLS Study Group Rating Scale scores were negatively correlated with apnea-hypopnea index and a nadir peripheral oxygen saturation during sleep. The presence of RLS was more likely to be associated with symptoms of depression, insomnia, and daytime sleepiness after controlling for confounding variables, but only in men. CONCLUSIONS: RLS is frequently noted in combination with OSA, with a female preponderance. The severities of OSA and RLS may be negatively associated. In patients with OSA, sex-related differences in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness warrant further investigations.

Mer tyrosine kinase regulates bone metabolism, and its deficiency partially ameliorates periodontitis- and ovariectomy-induced bone loss in mice.

Bone homeostasis is maintained by tightly coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. In the present report, the role of Mer tyrosine kinase (MerTK) in bone metabolism was investigated. The expression of MerTK decreased upon BMP2 stimulation of osteoblast precursors. The femurs of Mertk-deficient mice showed significantly increased bone volume with concomitant increase of bone formation and reduction in bone resorption. These bone phenotypes were attributed to the increased osteoblast differentiation and mineralization accounted by the enhanced ß-catenin and Smad signaling in the absence of MerTK in osteoblast precursors. Although the Mertk-deficient bone marrow macrophages were predisposed to enhanced osteoclast differentiation via augmented Ca2+-NFATc1 signaling, the dramatic increase of Tnfsf11b/Tnfsf11 (Opg/Rankl) ratio in Mertk knockout bones and osteoblast precursors corroborated the reduction of osteoclastogenesis in Mertk deficiency. In ligature-induced periodontitis and ovariectomy models, the bone resorption was significantly attenuated in Mertk-deficient mice compared with wild-type control. Taken together, these data indicate novel role of MerTK in bone metabolism and suggest a potential strategy targeting MerTK in treating bone-lytic diseases including periodontitis and osteoporosis.

Attention-deficit hyperactivity disorder in adults with epilepsy: An indirect relationship with suicide risk.

PURPOSE: Studies on attention-deficit hyperactivity disorder (ADHD) are scarce in adults with epilepsy. This study aimed to investigate the risk factors for ADHD and determine whether ADHD is directly associated with the risk of suicide in adults with epilepsy. METHODS: ADHD was assessed using the Structured Clinical Interview for the DSM-5 Disorders Clinical Version. The Mini International Neuropsychiatric Interview (MINI) Plus 5.0.0, Neurological Disorders Depression Inventory for Epilepsy (NDDIE), and Generalized Anxiety Disorder-7 (GAD-7) were also used. Suicide risk was defined as a MINI suicidality score of ≥ 1. Stepwise logistic regression and mediation analyses were conducted. RESULTS: Of the 157 adults with epilepsy, 19 (12.1 %) were diagnosed with ADHD, including inattentive (5.7 %), hyperactive (3.8 %), and combined (2.5 %) types. Thirty-two subjects (20.4 %) had a risk of suicide. ADHD was insignificantly associated with any epilepsy-related factors. The diagnosis of ADHD was not associated with suicide risk independent of NDDIE ≥ 14 and GAD-7 ≥ 7. Mediation effects of ADHD on suicidality using NDDIE ≥ 14 (odds ratio [OR] 2.850, 95 % confidence interval [CI] 1.398-5.811, p = 0.004) or GAD-7 ≥ 7 (OR 3.240, 95 % CI 1.537-6.828, p = 0.002) were statistically significant, with the proportion mediated being 84.5 % or 92.0 % of the total ADHD effect, respectively. These models were adjusted for age, sex, and composite epilepsy severity scores. CONCLUSIONS: ADHD was diagnosed in 12.1% of adults with epilepsy and was not associated with any epilepsy-related factors. ADHD was indirectly associated with the risk of suicide resulting from depression and anxiety in adults with epilepsy.

B. longum CKD1 enhances the efficacy of anti-diabetic medicines through upregulation of IL- 22 response in type 2 diabetic mice.

The gut microbiota plays a pivotal role in metabolic disorders, notably type 2 diabetes mellitus (T2DM). In this study, we investigated the synergistic potential of combining the effects of Bifidobacterium longum NBM7-1 (CKD1) with anti-diabetic medicines, LobeglitazoneⓇ (LO), SitagliptinⓇ (SI), and MetforminⓇ (Met), to alleviate hyperglycemia in a diabetic mouse model. CKD1 effectively mitigated insulin resistance, hepatic steatosis, and enhanced pancreatic ß-cell function, as well as fortifying gut-tight junction integrity. In the same way, SI-CKD1 and Met- CKD1 synergistically improved insulin sensitivity and prevented hepatic steatosis, as evidenced by the modulation of key genes associated with insulin signaling, ß-oxidation, gluconeogenesis, adipogenesis, and inflammation by qRT-PCR. The comprehensive impact on modulating gut microbiota composition was observed, particularly when combined with MetforminⓇ. This combination induced an increase in the abundance of Rikenellaceae and Alistipes related negatively to the T2DM incidence while reducing the causative species of Cryptosporangium, Staphylococcaceae, and Muribaculaceae. These alterations intervene in gut microbiota metabolites to modulate the level of butyrate, indole-3-acetic acid, propionate, and inflammatory cytokines and to activate the IL-22 pathway. However, it is meaningful that the combination of B. longum NBM7-1(CKD1) reduced the medicines' dose to the level of the maximal inhibitory concentrations (IC50). This study advances our understanding of the intricate relationship between gut microbiota and metabolic disorders. We expect this study to contribute to developing a prospective therapeutic strategy modulating the gut microbiota.

A Novel Fabrication of Heterogeneous Saponified Poly(Vinyl Alcohol)/Pullulan Blend Film for Improved Wound Healing Application.

In this study, a novel film of poly(vinyl alcohol) (PVA)/pullulan (PULL) with improved surface characteristics was prepared from poly(vinyl acetate) (PVAc)/PULL blend films with various mass ratios after the saponification treatment in a heterogeneous medium. According to proton nuclear magnetic resonance (1H-NMR), Fourier transform infrared, and X-ray diffraction results, it was established that the successful fabrication of saponified PVA/PULL (100/0, 90/10, and 80/20) films could be obtained from PVAc/PULL (100/0, 90/10, and 80/20) films, respectively, after 72 h saponification at 50 °C. The degree of saponification calculated from 1H-NMR analysis results showed that fully saponified PVA was obtained from all studied films. Improved hydrophilic characteristics of the saponified films were revealed by a water contact angle test. Moreover, the saponified films showed improved mechanical behavior, and the micrographs of saponified films showed higher surface roughness than the unsaponified films. This kind of saponified film can be widely used for biomedical applications. Moreover, the reported saponified film dressing extended the lifespan of dressing as determined by its self-healing capacity and considerably advanced in vivo wound-healing development, which was attributed to its multifunctional characteristics, meaning that saponified film dressings are promising candidates for full-thickness skin wound healing.

Atypical formations of gintonin lysophosphatidic acids as new materials and their beneficial effects on degenerative diseases.

Fresh ginseng is prone to spoilage due to its high moisture content. For long-term storage, most fresh ginsengs are dried to white ginseng (WG) or steamed for hours at high temperature/pressure and dried to form Korean Red ginseng (KRG). They are further processed for ginseng products when subjected to hot water extraction/concentration under pressure. These WG or KRG preparation processes affect ginsenoside compositions and also other ginseng components, probably during treatments like steaming and drying, to form diverse bioactive phospholipids. It is known that ginseng contains high amounts of gintonin lysophosphatidic acids (LPAs). LPAs are simple lipid-derived growth factors in animals and humans and act as exogenous ligands of six GTP-binding-protein coupled LPA receptor subtypes. LPAs play diverse roles ranging from brain development to hair growth in animals and humans. LPA-mediated signaling pathways involve various GTP-binding proteins to regulate downstream pathways like [Ca2+]i transient induction. Recent studies have shown that gintonin exhibits anti-Alzheimer's disease and anti-arthritis effects in vitro and in vivo mediated by gintonin LPAs, the active ingredients of gintonin, a ginseng-derived neurotrophin. However, little is known about how gintonin LPAs are formed in high amounts in ginseng compared to other herbs. This review introduces atypical or non-enzymatic pathways under the conversion of ginseng phospholipids into gintonin LPAs during steaming and extraction/concentration processes, which exert beneficial effects against degenerative diseases, including Alzheimer's disease and arthritis in animals and humans via LPA receptors.

Structural Identification of Ginsenoside Based on UPLC-QTOF-MS of Black Ginseng (Panax Ginseng C.A. Mayer).

Black ginseng (BG) is processed ginseng traditionally made in Korea via the steaming and drying of ginseng root through three or more cycles, leading to changes in its appearance due to the Maillard reaction on its surface, resulting in a dark coloration. In this study, we explored markers for differentiating processed ginseng by analyzing the chemical characteristics of BG. We elucidated a new method for the structural identification of ginsenoside metabolites and described the features of processed ginseng using UPLC-QTOF-MS in the positive ion mode. We confirmed that maltose, glucose, and fructose, along with L-arginine, L-histidine, and L-lysine, were the key compounds responsible for the changes in the external quality of BG. These compounds can serve as important metabolic markers for distinguishing BG from conventionally processed ginseng. The major characteristics of white ginseng, red ginseng, and BG can be distinguished based on their high-polarity and low-polarity ginsenosides, and a precise method for the structural elucidation of ginsenosides in the positive ion mode is presented.

Iridoid Glycosides and Coumarin Glycoside Derivatives from the Roots of Nymphoides peltata and Their In Vitro Wound Healing Properties.

Nymphoides peltata has been used as a medicinal herb in traditional medicines to treat strangury, polyuria, and swelling. The phytochemical investigation of the MeOH extract of N. peltata roots led to the isolation of three iridoid glycosides and three coumarin glycoside derivatives, which were characterized as menthiafolin (1), threoninosecologanin (2), callicoside C (3), and scopolin (4), as well as two undescribed peltatamarins A (5) and B (6). The chemical structures of the undescribed compounds were determined by analyzing their 1 dimensional (D) and 2D nuclear magnetic resonance (NMR) spectra and using high-resolution (HR)-electrospray ionization mass spectroscopy (ESI-MS), along with the chemical reaction of acid hydrolysis. The wound healing activities of the isolated compounds 1-6 were evaluated using a HaCaT cell scratch test. Among the isolates, scopolin (4) and peltatamarin A (5) promoted HaCaT cell migration over scratch wounds, and compound 5 was the most effective. Furthermore, compound 5 significantly promoted cell migration without adversely affecting cell proliferation, even when treated at a high dose (100 µM). Our results demonstrate that peltatamarin A (5), isolated from N. peltata roots, has the potential for wound healing effects.

Developmental roles of glomerular epithelial protein-1 in mice molar morphogenesis.

Glomerular epithelial protein-1 (Glepp1), a R3 subtype family of receptor-type protein tyrosine phosphatases, plays important role in the activation of Src family kinases and regulates cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, we firstly examined the functional evaluation of Glepp1 in tooth development and morphogenesis. The precise expression level and developmental function of Glepp1 were examined by RT-qPCR, in situ hybridization, and loss and gain of functional study using a range of in vitro organ cultivation methods. Expression of Glepp1 was detected in the developing tooth germs in cap and bell stage of tooth development. Knocking down Glepp1 at E13 for 2 days showed the altered expression levels of tooth development-related signaling molecules, including Bmps, Dspp, Fgf4, Lef1, and Shh. Moreover, transient knock down of Glepp1 revealed alterations in cellular physiology, examined by the localization patterns of Ki67 and E-cadherin. Similarly, knocking down of Glepp1 showed disrupted enamel rod and interrod formation in 3-week renal transplanted teeth. In addition, due to attrition of odontoblastic layers, the expression signals of Dspp and the localization of NESTIN were almost not detected after knock down of Glepp1; however, their expressions were increased after Glepp1 overexpression. Thus, our results suggested that Glepp1 plays modulating roles during odontogenesis by regulating the expression levels of signaling molecules and cellular events to achieve the proper structural formation of hard tissue matrices in mice molar development.

Functional modulation of lysophosphatidic acid type 2 G-protein coupled receptor facilitates alveolar bone formation.

Lipid biosynthesis is recently studied its functions in a range of cellular physiology including differentiation and regeneration. However, it still remains to be elucidated in its precise function. To reveal this, we evaluated the roles of lysophosphatidic acid (LPA) signaling in alveolar bone formation using the LPA type 2 receptor (LPAR2) antagonist AMG-35 (Amgen Compound 35) using tooth loss without periodontal disease model which would be caused by trauma and usually requires a dental implant to restore masticatory function. In this study, in vitro cell culture experiments in osteoblasts and periodontal ligament fibroblasts revealed cell type-specific responses, with AMG-35 modulating osteogenic differentiation in osteoblasts in vitro. To confirm the in vivo results, we employed a mouse model of tooth loss without periodontal disease. Five to 10 days after tooth extraction, AMG-35 facilitated bone formation in the tooth root socket as measured by immunohistochemistry for differentiation markers KI67, Osteocalcin, Periostin, RUNX2, transforming growth factor beta 1 (TGF-ß1) and SMAD2/3. The increased expression and the localization of these proteins suggest that AMG-35 elicits osteoblast differentiation through TGF-ß1 and SMAD2/3 signaling. These results indicate that LPAR2/TGF-ß1/SMAD2/3 represents a new signaling pathway in alveolar bone formation and that local application of AMG-35 in traumatic tooth loss can be used to facilitate bone regeneration and healing for further clinical treatment.

Toxicity of Aged Paint Particles to Soil Ecosystems: Insights from Caenorhabditis elegans.

Despite the extensive global consumption of architectural paint, the toxicological effects of aged exterior paint particles on terrestrial biota remain largely uncharacterized. Herein, we assessed the toxic effect of aged paint particles on soil environments using the nematode Caenorhabditis elegans (C. elegans) as a test organism. Various types of paint particles were generated by fragmentation and sequential sieving (500-1000, 250-500, 100-250, 50-100, 20-50 µm) of paint coatings collected from two old residential areas. The paint particles exerted different levels of toxicity, as indicated by a reduction in the number of C. elegans offspring, depending on their size, color, and layer structure. These physical characteristics were found to be closely associated with the chemical heterogeneity of additives present in the paint particles. Since the paint particle sizes were larger than what C. elegans typically consume, we attributed the toxicity to leachable additives present in the paint particles. To assess the toxicity of these leachable additives, we performed sequential washings of the paint particles with distilled water and ethanol. Ethanol washing of the paint particles significantly reduced the soil toxicity of the hydrophobic additives, indicating their potential environmental risk. Liquid chromatography-mass spectrometry analysis of the ethanol leachate revealed the presence of alkyl amines, which exhibited a high correlation with the toxicity of the paint particles. Further toxicity testing using an alkyl amine standard demonstrated that a paint particle concentration of 1.2% in soil could significantly reduce the number of C. elegans offspring. Our findings provide insights into the potential hazards posed by aged paint particles and their leachable additives in the terrestrial environment.

A perspective on the role of physiological stresses in cancer, diabetes and cognitive disease as environmental diseases.

With rapid industrialization, urbanization, and climate change, the impact of environmental factors on human health is becoming increasingly evident and understanding the complex mechanisms involved is vital from a healthcare perspective. Nevertheless, the relationship between physiological stress resulting from environmental stressors and environmental disease is complex and not well understood. Chronic exposure to environmental stressors, such as air and water contaminants, pesticides, and toxic metals, has been recognized as a potent elicitor of physiological responses ranging from systemic inflammation to immune system dysregulation causing or progressing environmental diseases. Conversely, physiological stress can exacerbate susceptibility to environmental diseases. Stress-induced alterations in immune function and hormonal balance may impair the ability to detoxify harmful substances and combat pathogens. Additionally, prolonged stress can impact lifestyle choices, leading to harmful behaviors. Understanding the link between physiological stress and environmental disease requires a systematic, multidisciplinary approach. Addressing this complex relationship necessitates the establishment of a global research network. This perspective discusses the intricate interplay between physiological stress and environmental disease, focusing on common environmental diseases, cancer, diabetes, and cognitive degeneration. Furthermore, we highlight the intricate and reciprocal nature of the connection between physiological stress and these environmental diseases giving a perspective on the current state of knowledge as well as identifying where further information is necessary. Recognizing the role of physiological stress in environmental health outcomes will aid in the development of comprehensive strategies to safeguard public health and promote ecological balance.

3‴-O-Foliamenthoyl-Rutin, a New Flavonoid Glycoside from the Roots of Nymphoides peltata.

Nymphoides peltata (Menyanthaceae) has been used as a medicinal herb in traditional medicines to treat conditions such as strangury, polyuria, swelling, and as a diuretic and antipyretic. In our ongoing research to discover novel structural and/or biological natural products in natural resources, five flavonoids, quercetin (1), quercitrin (2), isoquercetin (3), quercetin-3-O-vicianoside (4), and rutin (5), as well as a new flavonoid glycoside, 3‴-O-foliamenthoyl-rutin (6), were isolated from the MeOH extract of N. peltata roots. The chemical structure of the new compound (6) was determined by analyzing 1D and 2D NMR spectra and high-resolution (HR) electrospray ionization mass spectroscopy (ESIMS), along with a chemical reaction. The wound-healing activities of the isolated compounds (1-6) were evaluated using a HaCaT cell scratch test. Among the isolates, isoquercetin (3), quercetin-3-O-vicianoside (4), and 3‴-O-foliamenthoyl-rutin (6) promoted HaCaT cell migration over scratch wounds, with compound 4 being the most effective. Our findings provide experimental data supporting the potential of quercetin-3-O-vicianoside (4) as a wound-healing agent.

Newly isolated Lactobacillus paracasei strain modulates lung immunity and improves the capacity to cope with influenza virus infection.

BACKGROUND: The modulation of immune responses by probiotics is crucial for local and systemic immunity. Recent studies have suggested a correlation between gut microbiota and lung immunity, known as the gut-lung axis. However, the evidence and mechanisms underlying this axis remain elusive. RESULTS: In this study, we screened various Lactobacillus (L.) strains for their ability to augment type I interferon (IFN-I) signaling using an IFN-α/ß reporter cell line. We identified L. paracasei (MI29) from the feces of healthy volunteers, which showed enhanced IFN-I signaling in vitro. Oral administration of the MI29 strain to wild-type B6 mice for 2 weeks resulted in increased expression of IFN-stimulated genes and pro-inflammatory cytokines in the lungs. We found that MI29-treated mice had significantly increased numbers of CD11c+PDCA-1+ plasmacytoid dendritic cells and Ly6Chi monocytes in the lungs compared with control groups. Pre-treatment with MI29 for 2 weeks resulted in less weight loss and lower viral loads in the lung after a sub-lethal dose of influenza virus infection. Interestingly, IFNAR1-/- mice did not show enhanced viral resistance in response to oral MI29 administration. Furthermore, metabolic profiles of MI29-treated mice revealed changes in fatty acid metabolism, with MI29-derived fatty acids contributing to host defense in a Gpr40/120-dependent manner. CONCLUSIONS: These findings suggest that the newly isolated MI29 strain can activate host defense immunity and prevent infections caused by the influenza virus through the gut-lung axis. Video Abstract.

Anti-Wrinkling Effect of 3,4,5-tri-O-caffeoylquinic Acid from the Roots of Nymphoides peltata through MAPK/AP-1, NF-κB, and Nrf2 Signaling in UVB-Irradiated HaCaT Cells.

Nymphoides peltata has been widely used pharmacologically in traditional Chinese medicine to treat heat strangury and polyuria. The aim of this study was to isolate the bioactive components from N. peltata and evaluate their potential use as antioxidant and anti-wrinkle agents. Phytochemical investigation of the methanolic extract of N. peltata roots led to the isolation of 15 compounds (1-15), which were structurally determined as α-spinasterol (1), 3-O-ß-D-glucopyranosyl-oleanolic acid 28-O-ß-D-glucuronopyranoside (2), 4-hydroxybenzoic acid (3), protocatechuic acid (4), vanillic acid (5), p-coumaric acid (6), caffeic acid (7), ferulic acid (8), neochlorogenic acid (neo-CQA) (9), chlorogenic acid (CQA) (10), cryptochlorogenic acid (crypto-CQA) (11), isochlorogenic acid B (3,4-DCQA) (12), isochlorogenic acid A (3,5-DCQA) (13), isochlorogenic acid C (4,5-DCQA) (14), and 3,4,5-tri-O-caffeoylquinic acid (TCQA) (15). Of these 15 compounds, compound 2 was a new oleanane saponin, the chemical structure of which was characterized by 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data and high-resolution electrospray ionization mass spectrometry (HRESIMS), as well as chemical reaction. Biological evaluation of the isolated compounds revealed that 3,4,5-tri-O-caffeoylquinic acid (TCQA) significantly improved Nrf2 levels in an Nrf2-ARE reporter HaCaT cell screening assay. TCQA was found to potently inhibit the Nrf2/HO-1 pathway and to possess strong anti-wrinkle activity by modulating the MAPK/NF-κB/AP-1 signaling pathway and thus inhibiting MMP-1 synthesis in HaCaT cells exposed to UVB. Our results suggest that TCQA isolated from N. peltata might be useful for developing effective antioxidant and anti-wrinkle agents.

Tricin-enriched Zizania latifolia ameliorates non-alcoholic fatty liver disease through AMPK-dependent pathways.

This study aimed to identify and elucidate the mechanism underlying the protective effect of tricin-enriched Zizania latifolia (Z. latifolia) extract (ETZL) against free fatty acid (FFA)-induced lipid accumulation in vitro and non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet and fructose diet (HFD/F) in vivo. ETZL treatment significantly lowered body weight gain and decreased adipose tissue, lipid, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels in HFD/F-fed mice. ETZL acted on phosphorylated acetyl-CoA carboxylase (ACC) and anti-peroxisome proliferator-activated receptor α (PPARα) by activating the adenosine monophosphate-activated protein kinase (AMPK) pathway and inhibiting sterol regulatory element-binding proteins-1 (SREBP)/fatty acid synthase (FAS) signaling to inhibit de novo adipogenesis and increase fatty acid oxidation. In addition, treatment with ETZL increased nuclear factor erythroid-2-related factor 2 (Nrf2) levels to activate the antioxidant pathway. FFA-induced oxidative stress and fatty acid accumulation in HepG2 cells confirmed the improvement in fat accumulation through the AMPK and Nrf2 pathway activities of ETZL. These results suggest that ETZL ameliorates NAFLD by regulating lipid metabolism and defending against oxidative stress via AMPK-dependent pathways.

Quantitative and Qualitative Analysis of Neurotransmitter and Neurosteroid Production in Cerebral Organoids during Differentiation.

In the human brain, neurophysiological activity is modulated by the movement of neurotransmitters and neurosteroids. To date, the similarity between cerebral organoids and actual human brains has been evaluated using comprehensive multiomics approaches. However, a systematic analysis of both neurotransmitters and neurosteroids from cerebral organoids has not yet been reported. Here, we performed quantitative and qualitative assessments of neurotransmitters and neurosteroids over the course of cerebral organoid differentiation. Our multiomics approaches revealed that the expression levels of neurotransmitter-related proteins and RNA, including neurosteroids, increase as cerebral organoids mature. We also found that the electrophysiological activity of human cerebral organoids increases in tandem with the expression levels of both neurotransmitters and neurosteroids. Our study demonstrates that the expression levels of neurotransmitters and neurosteroids can serve as key factors in evaluating the maturity and functionality of human cerebral organoids.

Combined Treatment of Mori folium and Mori Cortex Radicis Ameliorate Obesity in Mice via UCP-1 in Brown Adipocytes.

Mori Folium (Morus alba leaf, MF) and Mori Cortex Radicis (Morus alba root cortex, MR) have been studied for their anti-obesity effects by enhancing the browning process and inhibiting adipogenesis. However, important aspects of their protective mechanisms have not been thoroughly investigated, which could aid in developing functional food. Thus, this study aims to determine the synergistic effects of MF and MR against obesity and its associated mechanisms. In an in vitro cell culture model of brown adipocytes, a 1:1 mixture of MF and MR showed a synergistic effect on the expression of brown adipocyte-specific genes, including Ucp-1, Ppargc1a, Cbp/p300-interacting transactivator (Cited), Prdm16, Tbx1, and Fgf21 compared with either MF- or MR-treated conditions. Moreover, they demonstrated the involvement of cAMP and Ca2+ in induction of brown adipocyte-specific genes. In an in vivo model using HFD-fed mice, MF/MR significantly inhibited weight gain, plasma cholesterol, LDL, TG content, fat mass, and adipocyte size. Furthermore, MF/MR inhibited morphological alteration and the expressions of fatty acid synthesis genes such as Srebp1 and Fasn in the white adipose tissue. Thermogenesis genes were recovered in the brown adipose tissue with MF/MR supplementation, indicating that MF/MR regulated adipocytic dysmetabolism where AMPK signaling is involved. In conclusion, these results suggested that MF/MR regulates brown and beige adipocyte processes, providing one of the preventive functional food/herbal medicines against obesity and its associated metabolic diseases.